1. Field of the Invention
The present invention relates to nonionic vitamin E derivatives capable of forming polymeric amphiphilic vesicles and to a method for the preparation thereof. More particularly, it relates to nonionic vitamin E or polyethoxylated vitamin E derivatives capable of forming polymeric amphiphilic vesicles which show an excellent thermodynamic stability, a compatibility in the living body and a physiological activity such as anti-oxidative effect, and to a method for the preparation thereof, and to polymeric amphiphilic vesicles made therefrom.
2. Description of the Prior Art
Various oily materials such as triglycerides, fatty acid esters or paraffins have been widely used as emollients in cosmetics and skin ointments for external applications, in order to prevent the evaporation of moisture from the skin. However, the cosmetics or skin ointments containing these oily materials further require an use of surfactants, in order to compensate poor compatibility thereof with water or water miscible components which are used as a base component for the cosmetics and skin ointments.
A surfactant is an amphiphilic or amphiphatic molecule having both a lyophobic group and a lyophilic group. That is, it consists of a long alkyl chain containing polar groups. Also, surfactant show a surface activity in solutions and forms aggregates of molecules or ions which are called micelles, when the concentration of the surfactant solute in the bulk of the solution exceeds a critical value, the so-called critical micelle concentration. The micelles may have spherical, cylindrical or plate shapes and can solubilize water-insoluble materials in the aqueous solution.
Besides, there are many natural amphiphilic biological compounds such as glycolipids, proteins, phospholipids, saponins and bile acids. These compounds are referred to "bio-surfactants", due to their source origin and surface active property. Because of surface activity, they can be easily solubilized in water and the other aqueous solutions so that they may exhibit effectively their physiological activities and make an absorption of other materials easy. In particular, phospholipids are components of the membrane lipid and can form liposomes easily since they have a hydrophobic group consisted of two aliphatic chains. Also, they have an excellent safety and moisture retention activity since they are constituent components of the biological cells. However, phospholipids may be easily oxidized to form peroxides due to the double bondings in the molecule and thereby causing damages to the cells. Consequently, they may promote the aging.
Therefore, there have been extensive studies and discussions for the development of a new material capable of forming vesicles similar to liposome formed by the phospholipids.
Since surfactants can have a vesicle-forming ability only when it has two alkyl chains and a balanced hydrophobic and hydrophilic property, the research for surfactants has been concentrated on the development of synthetic amphiphilic compounds.
J. M. Gebicki and M. Hicks reported in 1975 for the first time the formation of bilayered-membrane structure of the vesicles formed by using synthetic amphiphilic materials. This bilayered-membrane structure was formed by shaking a thin film of oleic acid and linoleic acid in an aqueous buffer. However, this closed membrane structure of bilayer is only stable in pH 6.about.8 and can not be concentrated by, for example centrifugation.
Thereafter, Kunitake et al. reported vesicles formed by dispersing of dialkyldimethylammonium and dihexadecylphosphate by ultrasonic treatment. The obtained vesicles are stable in the over pH range. However, these synthetic surfactant vesicles have a poor thermodynamic stability and may be easily agglutinated and then precipitated during a long term storage. This restricts the application of synthetic surfactant vesicles.
Recently, the polymerization of vesicles was proposed to improve the stability of synthetic vesicles. Besides, the "ploysoap" which is a polymerized amphiphilic molecules having a single alkyl chain had been also reported.
Therefore, the present inventors have conducted extensive studies to develop new polymeric amphiphilic vesicles. Their studies based on the fact that the vitamin E or polyethoxylated vitamin E derivatives have an excellent compatibility in the living body, surfactantivity, anti-oxidative action such as protective action against oxidation or UV in the skin or hair, and anti-inflammatory action, as well as have a sufficient hydrophobicity and orientation property to be served as hydrophobic group for forming vesicles. As a result, they proposed cationic vitamin E or polyethoxylated vitamin E derivatives obtained by introducing a cationic group of quaternary nitrogen into vitamin E or polyethoxylated vitamin E, and polymeric amphiphilic vesicles made therefrom. As expected, the proposed cationic vitamin E or polyethoxylated vitamin E derivatives have an excellent vesicles-forming ability. However, due to their cationic property, they showed a bad compatibility with anionic or amphipathic components in the living body. On the basis of this failure, they again proposed nonionic vitamin E or polyethoxylated vitamin E derivatives obtained by introducing acrylate, methacrylate or crotonate derivatives into vitamin E or polyethoxylated vitamin E, and polymeric amphiphilic vesicles made therefrom. However, the nonionic derivatives lack an anti-oxidative action preventing the oxidation of physiological active materials.
Under this circumstance, the present inventors have made research to provide a solution for the above problem. As a result, they found that nonionic polymeric amphiphilic vesicles could be obtained by controlling the reaction temperature and the amount of reactants in introducing allyl derivatives containing an amino group into vitamin E or polyethoxylated vitamin E derivatives. They proved that the proposed nonionic vesicles show an excellent thermodynamic stability, a compatibility in the living body and a physiological activity such as anti-oxidative effect.